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International Journal of Hyperthermia

ISSN: 0265-6736 (Print) 1464-5157 (Online) Journal homepage: https://www.tandfonline.com/loi/ihyt20

Design and simulation of novel laparoscopic renaldenervation system: a feasibility study

Eunbi Ye, Jinhwan Baik, Seunghyun Lee, Seon Young Ryu, Sunchoel Yang,Eue-Keun Choi, Won Hoon Song, Hyeong Dong Yuk, Chang Wook Jeong &Sung-Min Park

To cite this article: Eunbi Ye, Jinhwan Baik, Seunghyun Lee, Seon Young Ryu, Sunchoel Yang,Eue-Keun Choi, Won Hoon Song, Hyeong Dong Yuk, Chang Wook Jeong & Sung-Min Park(2018) Design and simulation of novel laparoscopic renal denervation system: a feasibility study,International Journal of Hyperthermia, 35:1, 9-18, DOI: 10.1080/02656736.2018.1468037

To link to this article: https://doi.org/10.1080/02656736.2018.1468037

© 2018 The Author(s). Published withlicense by Taylor & Francis Group, LLC

Published online: 18 May 2018.

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Design and simulation of novel laparoscopic renal denervation system: afeasibility study

Eunbi Yea , Jinhwan Baika, Seunghyun Leea, Seon Young Ryua, Sunchoel Yangb, Eue-Keun Choic,Won Hoon Songd, Hyeong Dong Yukd, Chang Wook Jeongd and Sung-Min Parka

aDepartment of Creative IT Engineering, POSTECH, Pohang, Republic of Korea; bDepartment of Prototype Production, Osong MedicalInnovation Foundation, Chungbuk, Republic of Korea; cDepartment of Internal Medicine, Seoul National University Hospital, Seoul, Republicof Korea; dDepartment of Urology, Seoul National University Hospital, Seoul, Republic of Korea

ABSTRACTPurpose: In this study, we propose a novel laparoscopy-based renal denervation (RDN) system fortreating patients with resistant hypertension. In this feasibility study, we investigated whether our pro-posed surgical instrument can ablate renal nerves from outside of the renal artery safely and effectivelyand can overcome the depth-related limitations of the previous catheter-based system with less dam-age to the arterial walls.Method: We designed a looped bipolar electrosurgical instrument to be used with laparoscopy-basedRDN system. The tip of instrument wraps around the renal artery and delivers the radio-frequency (RF)energy. We evaluated the thermal distribution via simulation study on a numerical model designedusing histological data and validated the results by the in vitro study. Finally, to show the effectivenessof this system, we compared the performance of our system with that of catheter-based RDN systemthrough simulations.Results: Simulation results were within the 95% confidence intervals of the in vitro experimentalresults. The validated results demonstrated that the proposed laparoscopy-based RDN system producesan effective thermal distribution for the removal of renal sympathetic nerves without damaging thearterial wall and addresses the depth limitation of catheter-based RDN system.Conclusions: We developed a novel laparoscope-based electrosurgical RDN method for hypertensiontreatment. The feasibility of our system was confirmed through a simulation study as well as in vitroexperiments. Our proposed method could be an effective treatment for resistant hypertension as wellas central nervous system diseases.

ARTICLE HISTORYReceived 11 December 2017Revised 27 March 2018Accepted 17 April 2018

KEYWORDSBiological modelling;hypertension; numericalsimulation; radiofrequencyablation; renal denervation

Introduction

Hypertension is a growing global public health problem due tomultiple reasons, including an aging population and the risingrates of obesity [1,2]. Approximately 10% of patients diagnosedwith hypertension have resistant hypertension, which isdefined as blood pressure that remains above the desired leveldespite treatment with three antihypertensive agents of differ-ent classes [1] and blood pressure that is controlled usingmore than four medications [2]. Resistant hypertension is a ser-ious condition leading to various life-threatening clinical com-plications, such as heart failure, stroke, renal failure and heartdisease [1,3]. Thus, treating resistant hypertension clinically isvery important for the patient’s longevity and quality of life.

Sympathetic nerves play an important role in long-termblood pressure regulation in humans [4,5]. The increasedsympathetic activity has been implicated as the primary pre-cursor of hypertension in both humans and in animal models[6]. Furthermore, there is growing evidence that abnormalrenal function in hypertension is due to the increased activity

of renal sympathetic nerves [7]. Thus, an open surgical pro-cedure to remove renal sympathetic nerves for treatinghypertension called Sympathectomy was employed in 1930[8–10]. Although this technique provided effective treatment,its use was discontinued because of its highly invasive natureand associated complications, such as perioperative morbid-ity, mortality and long-term complications [11,12].

Recently, a minimally invasive procedure called renaldenervation (RDN) system has been developed as an effect-ive method to remove renal nerves for treating resistanthypertension. The RDN procedure selectively removes thehyperactive renal sympathetic nerves using a radiofrequency(RF) ablation technique, thus controlling hypertension. Acatheter-based RDN system, a prominent representative sys-tem for the RDN procedure, has demonstrated promisingresults with minimal side effects in nonrandomized studiesand unblended randomised trials [13–15]. However, a recentphase-III randomized controlled trial, investigating the effi-cacy and safety of this procedure, have found that the cath-eter-based RDN is not effective and shows no improvement

CONTACT Sung-Min Park sungminpark@postech.ac.kr Department of Creative IT Engineering, POSTECH, Pohang 37673, Republic of Korea; Chang WookGeong drboss@gmail.com Department of Urology, Seoul National University Hospital, Seoul 03080, Republic of Korea� 2018 The Author(s). Published with license by Taylor & Francis Group, LLCThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,distribution, and reproduction in any medium, provided the original work is properly cited.

INTERNATIONAL JOURNAL OF HYPERTHERMIA2018, VOL. 35, NO. 1, 9–18https://doi.org/10.1080/02656736.2018.1468037

in outcomes of patients with resistant hypertension whencompared with the outcomes of the sham procedure [16].The primary limitation of the catheter-based RDN system,found through histopathological evaluation of the renalartery, is that the electrodes placed inside the lumen of theartery cannot deliver RF energy effectively to all the renalnerve bundles along the renal artery, especially to the nervespresent beyond 2mm from the lumen surface [17]. Sincesympathetic nerves are located at a distance of 0.5–10mmfrom the intima layer of the artery with approximately 31%of the nerves located between 2 and 10mm from the lume-n–intima interface [18,19], the catheter-based system couldnot deliver sufficient energy to treat the hyperactive nerves.Higher RF energy could be used to destroy these distantnerves but may severely damage the intima layer resulting inserious side effects, such as stenosis. The secondary limitationof the catheter-based approach is that it could not directlymonitor the temperature rise near the renal nerves outsidethe artery during or after the treatment.

In the absence of effective surgical treatment for resistanthypertension, a laparoscopic approach has been proposed asan alternative method to overcome the limitations of thecatheter approach [20]. According to Gerber et al. [20], thelaparoscopic approach is capable of removing nerves that aretypically not removed by RF-based catheter ablation. Theclaim by Gerber et al. is promising, there have been no stud-ies published to describe the surgical strategy or instrumentdesign for the effective laparoscopy-based RDN system. Inthis study, for the first time, we propose a laparoscopy-basedRDN system design that ablates the renal nerves from theexterior of the renal artery by wrapping it around. We dem-onstrate its feasibility of this system using the numericalmodel developed based on clinical data and validatedthrough extensive in vitro experiments. This system demon-strates the feasibility of the effective denervation of the renal

nerve present between 0.5 and 10mm from the arteriallumen. We confirmed the superiority of our system over thecatheter-based RDN system via simulations based on per-formance. Our results demonstrate that a practical laparo-scopic system could be developed for the surgical treatmentof resistant hypertension.

Methods

Proposed surgical system of laparoscopy-based RDN

Our surgical RF ablation plan is shown in Figure 1. The tis-sues surrounding the renal artery is excised from the dorsalside through trocars to expose the renal artery to allow easyaccess for the surgical instruments to perform RF ablation.The retroperitoneal approach using three trocars is minimallyinvasive and reduces the likelihood of complications becausethere is no peritoneal violation is involved.

Our surgical tip design objectives were threefold: (1) to com-pletely remove renal sympathetic nerves without damaging therenal artery, (2) to minimize the damage to the surrounding tis-sues by focusing RF heating within the contour of the wrappedelectrode, and (3) to be flexible enough to adapt to differentrenal artery sizes. Figure 2 shows the conceptual design of theproposed surgical instrument with a looped electrode thatmeets the desired design objectives. To localize the heatingproximal to the electrodes, the tip structure was configured tobe bipolar, wherein both electrodes were placed side by side.The RF current, which flows between the electrodes, rapidlyattenuates as the distance of the tissue from the electrodesincreases. To completely remove renal nerves distributedaround the artery, the electrode, which is the end part of thesurgical instrument, was designed to wrap around the renalartery such that RF energy is delivered to completely removesympathetic nerves distributed around the artery. As shown in

Figure 1. Schematic drawing of proposed laparoscopy-based RDN surgical approach.

10 E. YE ET AL.

Figure 2, a strip of highly conductive elastic material was placedunder the electrodes. Due to its elasticity, the tip remains flatwithin the case of the surgical instrument while entering thebody and starts to wrap around the artery when the tip ispushed out of the case at the surgical site. This elastic strip alsoallows the tip to fit to different sizes of the renal artery. In add-ition, the strip is made of highly conductive material to reducethe RF field radiating to the posterior part of the electrode dueto the electromagnetic shielding effect of electrically high con-ductive materials [21]. Therefore, with the metal strip, RF energyin the rear side of the electrode is minimized preventing anydamage to the normal tissues at the site.

Computational modelling

Tissue modellingIn our previous study, we analyzed the anatomical distributionof sympathetic nerve fibers around the renal artery using thenephrectomy tissues from humans. We showed that approxi-mately 31% of the renal sympathetic nerves are located beyond2mm from the arterial lumen [19]. To reflect our previous find-ings in tissue modelling, we developed a realistic three-dimen-sional (3D) numerical model based on the thinnest of the 174tissue slides obtained at 40lm intervals, from a representativetissue. Then, we developed a simplified simulation model shownin Figure 3(b). In this model, the renal artery diameter was5mm, the lumen diameter was 2mm, and the thickness of theblood vessel wall was 1.5mm. The four renal sympathetic nerveswere modelled at 2mm, 2.5mm, 3mm, and 3.5mm because90% of the nerve fibers are located within 4mm from theluminal surface of the renal artery, based on our histologicalstudies. In addition, to verify the RF field radiating to the outsideof the surgical tip, a renal vein located posterior to the renal

artery was modelled with an outer wall diameter of 10mm,lumen diameter of 8.6mm, and wall thickness of 0.7mm [22].

The surrounding tissue environment was modelled in twocases depending on the surgical approach. For the laparoscopy-based RDN system shown in Figure 4(a), the tissues betweenthe artery and electrodes were assigned as fat and nerves andthe surrounding environment outside the surgical instrumentwas assigned gaseous CO2, which is commonly used in laparo-scopic surgeries; because the perinephric fat and Gerota’s fasciaenclosing the kidney need to be incised via a laparoscopic sur-gical approach. For the catheter-based RDN system shown inFigure 4(b), the surrounding tissue was modelled as fat to rep-resent the catheter-based procedure. Table 1 lists the propertiesof the materials included in the simulation.

RF ablation tip modellingThe proposed RF ablation tip was simulated for RF energyand resulting heat distribution using the Sim4life

Figure 2. Concept design of the surgical instrument for laparoscopy-based RDN.

Figure 3. (a) A realistic computable 3D model generated by histological ana-lysis. (b) Simplified 3D phantom [mm]. The model includes the renal nerves andrenal arterial wall.

INTERNATIONAL JOURNAL OF HYPERTHERMIA 11

computational electromagnetic analysis software. The gapbetween the bipolar electrodes was 2mm, the width of thehighly conductive metal strip was 3mm, and the total widthof the tip was 5mm such that the surgical device can beinserted through the 5mm trocar that is commonly used in alaparoscopic procedure. While performing simulations, allconductive materials were assigned as stainless steel andinsulation materials were assigned as polyimide.

To compare the safety and efficacy between the catheter-and laparoscopy-based systems, a simplified 6 F catheter-based Symplicity Flex (Medtronic, Santa Rosa, CA, USA) withan outer diameter of 2mm and an inner diameter of 1.8mmwas modelled [23].

Numerical simulation setup

Computational calculation of the temperature distributionaround the electrodes and tissues during RF injection wasperformed using Sim4life V3.4 software (ZMT, Zurich,Switzerland). Sim4life is a simulation platform that providescomputational human phantoms with multi-physics solversand advanced tissue models. The multiphysics solvers includethe full electromagnetic wave, quasi-static electromagneticand thermodynamic solvers. This tool is useful for developingnovel devices, optimizing design parameters, increasing the

knowledge regarding energy delivery and determininginduced heating [24].

Computation of electric fieldsThe frequency of the source RF current was 1MHz, which isconsiderably less than the resonant frequency of 100MHz, asshown in Figure 5. Quasi-static electromagnetic solver wasused to calculate low-frequency electromagnetic problems[25] with the following equation:

r � ~�rØ ¼ 0 (1)

where ~e is the complex electric permittivity and Ø is a scalarpotential. The electromagnetic field was recorded to use as aheat source for the thermal simulations.

Figure 4. Finite element modelling: (a) laparoscopy-based RDN, (b) catheter-based RDN.

Table 1. Electrical and thermal properties of the materials.

q [kg/m3]a r [S/m]b j [W/m/K]c HR [W/m3/K]d

Blood 1049 0.659 0.517 709,090Blood vessel wall 1101 0.232 0.462 11160.7Nerve 1075 0.265 0.490 11642.5Fat 911 0.057 0.212 2012.8CO2 1.977 0 0.017 0GelSetting 1 950 0.23 0.605 0Setting 2 0.65

aq¼material density, br¼ electric conductivity, cj¼ thermal conductivity,dHR¼ heat-transfer rate.

Figure 5. Input impedance of the prototype electrode as a functionof frequency.

12 E. YE ET AL.

Temperature distribution computationThe temperature changes in the tissues during RF ablationwere calculated using the following Pennes bioheatEquation (2), which has been extensively used to solve com-putational bio-electromagnetic problems since its introduc-tion [26].

qc@T@t

¼ r � krTð Þ þ qQþ qS� qbqx T � Tbð Þ (2)

where q is the material density, c is the specific heat cap-acity, T is the tissue temperature, k is the thermal conductiv-ity, Q is the metabolic heat generation rate, S is the specificabsorption rate, and x is the perfusion rate. The term‘qbcbqw’ is sometimes referred as the heat-transfer rate (HR).The perfusion rate of blood was set at 10,000ml/min/kg [27]to examine the blood cooling effect according to the bloodperfusion rate.

Experimental validation setup

To validate the numerical simulation technique of the RFablation device, in vitro experiments were conducted, andthe results were extensively compared with the results of thesimulations performed under the same conditions. For the invitro experiments, we constructed a prototype tip and eval-uated the heating effects of the tip at nine measurementpoints. The experimental system for delivering RF energy tothe device and measuring the temperature profile during RFinjection is shown in Figure 6. The system comprised an RFgenerator (Tektronix, AFG3101), RF amplifier (Minicircuit, LZY-22þ), power sensor (Keysight, U2004A), and directional coup-ler (Minicircuit, ZABDC50–150HPþ). The system was con-trolled by the LabVIEW 2013 software. The prototype tipcomprised three layers: a metal strip, insulation and two elec-trodes placed 2mm apart to support bipolar mode. Stainlesssteel 304 (SUS304) was used for the construction of the elec-trodes and metal strip for RF blocking, and the plate wasinsulated using a polyimide film. The tip was24mm� 110mm, and the electrodes were 2mm� 100mm(Figure 7(a)).

The experiment was conducted with 6 L gel mixed withpolyacrylic acid and NaCl in a 160mm� 430mm� 170mmacrylic water tank. The gel had two conductivity settings as

shown in Table 1: 0.23 S/m (setting 1) and 0.65 S/m (setting2). The conductivities of the gels reflected those of the bloodvessel walls and blood, respectively, because they areaffected thermally during RDN. Dielectric properties of gelswere measured by a network analyzer (Keysight, E5061B).The input power was switched on for 6min [28] and then offfor 1min at 1MHz. The source was connected to the elec-trode via a coaxial cable.

Temperature distribution near the prototype tip wasmeasured using a fiber optic thermometry system (Luxtron,m600), which can minimize the potential electromagneticinterference (Figure 7(b)). Temperature probes were fixed atthe openings in the temperature probe holder that was fabri-cated using a 3D printer (3 D Systems, Project MJP 2500).The spacing between openings was 10mm along the x-axisand 2.5mm along both y- and z-axes to facilitate the meas-urement at different locations. The fixture holding tempera-ture probe kept the temperature sensors in position relativeto the electrodes for simultaneous temperature measure-ment. The experimental protocol is shown in Figure 8. Themeasurements were repeated six times for each gel settingin the three axial directions, thus resulting in 36 measure-ments. The electromagnetic simulations were performed withthe same initial parameters as in the experiments. The tem-perature data of both the simulation and validation experi-ments were normalised by the difference between the initialand average temperatures during the last 60 s of the power-on period.

Results

In this section, we validated the numerical model via invitro studies by comparing the simulated heating results ofthe simplified surgical device tip with the measured results

Figure 6. Experimental system for simulation validation.

Figure 7. (a) Schematic representation of a prototype tip. (b) Temperaturemeasurement setup. The tip is fixed by the fixture and is connected to coaxialcable. The temperature is inserted into through the holder and measures thetemperature on the tip. The temperature is measured at nine points, threepoints for each three axes.

INTERNATIONAL JOURNAL OF HYPERTHERMIA 13

under the same condition in vitro. We then use this vali-dated model to conduct extensive simulation studies forour prosed laparoscopy-based RDN tip design with thesimplified anatomical phantom that was constructed basedon histological analysis.

Simulation method validation

The simulated temperature distribution around the prototypetip is shown in Figure 9. The temporal temperature data inthe simulation results were extracted at the same pointsmeasured in the in vitro experiment. The similarity of thermalpatterns during RF ablation between the extracted tempera-ture in the simulations and the measured temperature in thein vitro studies for settings 1 and 2 are shown in Figure 10.The error bars denote ±2 standard deviations for each 60 stime interval, indicating a 95% confidence interval for therepeated experimental temperature measurements. InTable 2, time constants (s), average standard deviation (SD)and error values (E), calculated as the maximum differences

between the experimental and simulation results, and max-imum error (Max E) are presented for both the settings.The simulation results were within 95% confidence intervalsof the experimental results during the RF injection. The aver-age standard deviation was 0.0312, and the average errorwas 2.7%, indicating that the simulation results reflected theactual temperatures observed during experiments.

These validation results confirmed the excellent agree-ment between the simulation and experimental resultsexcept for a few discrepancies. These discrepancies arosebetween simulation and in vitro experiments due to the dif-ferences in placement of the temperature probe betweensimulation and in vitro experiments. The simulation resultswere based on the temperatures at the center of each open-ing. However, the temperature probe location could not befixed in the in vitro because the diameter of the temperatureprobe holder (1.2mm) was larger than that of the tempera-ture probe diameter (0.6mm). Figure 11 shows the best heatmatching results when the simulation results were obtainedwith the probe moving across the probe holder along the y-axis. With setting 1, the average error decreased from 2.9%to 1.9%, and with setting 2, the error decreased from 3.7% to2.8%. These results confirm that the source of discrepanciesbetween the simulations and the in vitro experiments mainlyarose due to the differences in the placement of the probeand not due to any other fundamental reasons, thus confirm-ing the credibility of the simulation results.

Heat effect on biological tissues

In vitro experiment results confirmed the validity of ournumerical simulation technique and we used this numericaltechnique to simulate the proposed device design in a sim-plified in vivo setting. We performed the thermal simulationon an anatomical phantom for 120 s to obtain the heatingpattern distribution within the phantom using our design.The temperature distributions are shown in Figures 12and 13. Figure 12 shows the normalized thermal distributionin tissues with the laparoscopy-based and catheter-basedsurgical instruments, where the edge of the red block is theluminal surface and the edge of the blue block is the outersurface of arterial wall. With the laparoscopy-based RDNdevice, the temperature decreased to approximately 50% ofthe peak temperature at the outer wall and to 30% of thepeak at the luminal surface (Figure 12(c)). With the catheter-

Figure 9. The temperature distribution in the prototype tip model. The model includes the surgical tip and gel. It was normalized with min-max scaling. The tem-poral temperature profiles were extracted at the same position where the temperature was measured in the experiment marked with white dots (X1, X2, X3, Y1, Y2,Y3, Z1, Z2, Z3).

Figure 8. Experimental validation protocol. Experiments were conducted withthe same protocol for setting 1 and setting 2, respectively.

14 E. YE ET AL.

based RDN device, the temperatures at outer surface andluminal surface of arterial wall were up to 95% and 85% ofthe peak temperature, respectively, despite the cooling effectof the blood flow as shown in Figure 12(d). When the tem-perature of the cell increases above 45 �C–50 �C, proteinbreakdown occurs, resulting in cell necrosis [29]. Based onthe simulation results obtained with the assumption that thepeak temperature generated at the electrode was 60 �C, wefound that for the laparoscopy-based device the temperatureincreased to 48 �C–58 �C at the sympathetic nerves, to 41.6 �Cat the outer wall of the artery and to 39.3 �C at the inner

wall of the artery. For the catheter-based device, under simi-lar conditions, the temperature increased to 46 �C–54 �C atthe renal sympathetic nerve, to 58.9 �C at the outer wall ofthe artery, and to 56.6 �C at the inner wall of the artery. Wefound that the both laparoscopic and catheter-based RDNmay result in necrosis at the nerve since the temperature risefor both cases are more than 45 �C. However, the results sug-gests that the laparoscopy-based system is safer since thetemperature at the inner wall is lower than 45 �C, while thecatheter-based system could cause serious damage to innerwalls, which results in serious side effects such as stenosis,since the temperature rise is more than 45 �C.

Thus, our simulation results clearly show that the laparos-copy-based approach would be safer while effectively elimi-nating the renal sympathetic nerves. Figure 13 shows thetemperature distribution as a function of blood perfusionrate for perfusion rates of 10,000, 5000, and 0ml/min/kg. Asshown in the graph, the temperature inside the arterydecreased as the blood perfusion rate increased, resulting inthe blood cooling effect. Thus, the lumen inside the arteryreceives drastically reduced heat from the bipolar electrodelocated outside the artery.

In the real laparoscopic surgery, the fat surrounding therenal artery are removed, the artery is exposed to allow thewrapping of the renal artery by the surgical tip, and renalvein locates very close to the artery. We modelled the renal

Figure 10. The temporal temperature at the nine measurement positions: (a–c) setting 1 (r¼ 0.23 S/m, e¼ 43), (d–f) setting 2 (r¼ 0.35 S/m, e¼ 72). The solidlines represent the simulation results, while the dot lines represent the experiment results. Each graph was normalized by the difference between the initial andaverage temperatures during the last 60 s of the power-on period.

Table 2. Comparison of experimental and 3-D simulation normalized tempera-ture profiles.

Setting Axis Method s [sec] SD E [%] Max E [%]

1r¼ 0.23 S/m, x Exp. 83 0.0320 2.8 13.9e¼ 43 Simul. 81

y Exp. 110 0.0285 2.9 9.9Simul. 116

z Exp. 171 0.0329 1.7 6.4Simul. 137

2r¼ 0.65 S/m, x Exp. 76 0.0348 3.3 10.3e¼ 72 Simul. 69

y Exp. 99 0.0222 3.7 13.1Simul. 112

z Exp. 150 0.0368 1.7 5.0Simul. 132

INTERNATIONAL JOURNAL OF HYPERTHERMIA 15

vein, which is located posterior to the surgical tip, to exam-ine the effects of heat radiation to the surrounding anatomy.Figure 14 plots the temperature at the renal vein with andwithout the insertion of metal strip that is posterior to theinstrument. The normalized graph demonstrates that thetemperature at the vein was slightly elevated without themetal strip while using our device, and thus, safety can beenhanced by reducing the heat radiated to the rear side ofthe instrument.

Discussion

In this study, we showed proof of concept of a newlydesigned laparoscopy-based RDN system through simula-tion study and validation experiments. The high level ofagreement between measured and simulated thermalresults confirm our findings. Simulation results confirmedthat the laparoscopy-based system can address the limita-tions of the catheter-based system in treating hypertension.The results of numerical simulations showed that heat dis-tributions induced by the electric fields are always greaterin regions closer to the electrodes. In addition, blood

perfusion inside the arteries causes a cooling effect result-ing in significantly reduced harmful effects compared tothe catheter-based approach. Thus, the laparoscopy-basedRDN approach, which includes placing the electrodes dir-ectly on the nerve outside the artery, can remove therenal nerves more safely and effectively than the catheter-based RDN approach, which includes positioning the elec-trodes inside the artery. The laparoscopic RDN system hasother advantages due to access from the outside of theartery. First, by wrapping the renal arteries completely bya surgical tip, the renal nerves can be completely removedregardless of the distance. Second, by inserting the therm-ometer into the surgical instruments, the temperature risein the nerves positioned outside the arteries can be moni-tored during the procedure allowing stable control andensuring safety and efficacy.

The main limitation of our study, however, is that weestablished the feasibility of our design mainly via simulationand in vitro studies. In the real-world environment, thebehavior of the system could be very different from thesesimulation results. Thus, as a next step of verification that iscloser to the real-world environment, we plan to conduct our

Figure 11. (a–b) Heat pattern matching (Y-component) when all the simulation results were obtained at the center of the temperature probe hole. (c–d) Heat pat-tern matching (Y-component) when the simulation results obtained with best position optimization in the hole. Each graph was normalized by the differencebetween the initial and average temperatures during the last 60 s of the power-on period.

16 E. YE ET AL.

study on an animal surgical model as well as ex vivo modelalong with histological examination to confirm RDN effective-ness and safety of surrounding tissue.

This laparoscopy-based method can change the paradigmof hypertension treatment, and it can also be extended fortreating many other diseases caused by abnormalities of thecentral nervous system, such as sleep apnea, depression andheart diseases. In addition, secondary complications could beprevented through improved primary treatment [1,2,30–33].When our laparoscopic surgical instrument is developed, itcould be applied to the robotic surgical system to establishless invasive and more accurate RDN method. Thus, thedevelopment of this novel laparoscopy-based RDN procedurecan be significantly beneficial for a wide variety of patientpopulations.

Conclusions

In this study, we proposed a novel laparoscopy-based elec-trosurgical RDN device for resistant hypertension treatment.The thermal distributions induced by this new surgical instru-ment was evaluated and compared with catheter-based RDNsystem using simulation method. The simulation results

Figure 12. Cross-sectional views of the heat distribution: (a) laparoscopy-basedRDN, (b) catheter-based RDN. Two-dimensional temperature profiles: (c) laparos-copy-based RDN, (d) catheter-based RDN (red block: renal arterial lumen, blueblocks: renal arterial wall, black line: position of the electrode). Each graph wasnormalized with min-max scaling, respectively.

Figure 13. Two-dimensional temperature profiles according to the blood perfu-sion rate (red block: renal arterial lumen, blue blocks: arterial wall). The graphwas normalized with min-max scaling.

Figure 14. Blocking thermal radiation to the renal vein using Nitinol (con-ductor): (a) without metal strip and (b) with metal strip. (c) Two-dimensionaltemperature profiles with or without metal strip (red block: renal arterial lumen,blue block: renal arterial wall, gray block: renal vein). Each data were normalizedwith minmax scaling, respectively.

INTERNATIONAL JOURNAL OF HYPERTHERMIA 17

showed that our device is safer and more effective than theexisting catheter-based systems. Our approach, is effective inblocking the sympathetic nerves located even beyond 2mmfrom the luminal surface, which are otherwise left untreatedby previous catheter-based RDN system. Our in vitro experi-mental results validated the simulation results. Going for-ward, we will conduct our study on an animal surgical modelalong with histological examination to confirm RDN effective-ness and safety of surrounding tissue. The success of this sys-tem will ultimately provide a safe and effective treatment forresistant hypertension and may also contribute toward thetreatment of refractory heart disease, and arterial fibrillation.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

This research was supported by the Ministry of Science and ICT (MSIT),Korea, under the ICT Consilience Creative Program [IITP-2018-2011-1-00783] supervised by the Institute for Information & CommunicationsTechnology Promotion (IITP), the Korea Health Technology R&D Projectthrough the Korea Health Industry Development Institute (KHIDI) fundedby the Ministry of Health & Welfare, Republic of Korea [grant number:HI17C1314], and under the Basic Science Research Program through theNational Research Foundation of Korea (NRF) funded by the Ministry ofScience and ICT [NRF-2017R1A5A1015596].

ORCID

Eunbi Ye http://orcid.org/0000-0002-5927-989XSung-Min Park http://orcid.org/0000-0002-8359-8110

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